The controls for TAS LHMT cards consist of two separate vials. One was designed to mimic a sample from a normal individual, and the second to mimic a sample from a patient with a prolonged clotting time due to administration of heparin. These controls are made with pig plasma. To make the controls as easy to use as possible for point-of-care testing, we chose the patented packaging system of Medtox, (Burlington, NC). This consists of a closed, crushable glass ampoule containing lyophilized plasma which is inside a plastic sleeve. The sleeve contains water for diluent and has a capped dropper top with a filter in the tip (to remove glass shards from the sample). The entire assembly is shrink wrapped with a label and plastic seal. To use, the ampoule is crushed inside the plastic sleeve, which allows the diluent to mix with the Ivophilized plasma. The mixture is reconstituted by shaking or vortexing the capped vial. The plastic seal and cap are removed and three drops of plasma suspension are discarded into a biohazard waste container (to eliminate the dilution effect of the diluent that is contained in the filter). A drop of the plasma suspension is added to a TAS LHMT card in an analyzer. The rest of the test procedure and the manner of signal production is identical to that for a patient sample.

AI/ML Overview

The provided text describes the TAS LHMT Controls, a device used for quality control of the TAS Analyzer and TAS LHMT cards in coagulation studies.

Here's an analysis of the acceptance criteria and the study that demonstrates device performance:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal "acceptance criteria" or specific thresholds the device must meet for approval. Instead, it demonstrates the device's performance through precision studies. The primary goal is to show that the TAS LHMT Controls perform "comparably" and are "substantially equivalent" to the predicate device (TAS HMT controls) and produce consistent clotting times within expected ranges.

Therefore, the "acceptance criteria" are implicitly derived from the reported precision (low CV%) for both normal and heparin controls, and the demonstration that the control produces clotting times "like that of a normal individual" and "mimics the response of a patient given a moderate level of heparin." The stability data (room temperature and freezer stability) also functions as a performance measure.

Characteristic	Acceptance Criteria (Implicit)	Reported Device Performance (TAS LHMT Controls)
Within-day Precision	Low Coefficient of Variation (CV%) for clotting times	Normal Control: Mean 151 sec, SD 1.7, CV 1.1%
		Heparin Control: Mean 296 sec, SD 9.8, CV 3.3%
Lot-to-lot Precision	Low Coefficient of Variation (CV%) across different lots	Normal Control (3 lots): Mean 152-153 sec, CV 1.0-2.3%
		Heparin Control (3 lots): Mean 293-296 sec, CV 3.7-5.7%
Mimicry of physiological states	Normal control produces clotting time like a normal individual; Heparin control mimics a patient with moderate heparin.	Normal control produced clotting time "like that of a normal individual"; Heparin control "mimics the response of a patient given a moderate level of heparin."
Stability (Room Temp)	Stable for a specified period (e.g., at least 6 weeks)	Stable for at least 6 weeks at 20-25°C indicating probable refrigerator stability of at least six months.
Stability (Reconstituted)	Stable for a specified short period	Reconstituted vials are stable for five minutes.
Stability (Freezing)	Little to no effect on performance	No significant difference in mean or CV produced by controls stored at -80°C compared to refrigerated vials.
Effect of Heating	Avoid significant increase in clotting time	Heating intact vials to 37°C for several days causes an increase in mean clotting time. (This is a condition to avoid, not a criterion to meet, showing understanding of limits).
Dispensing Angle	Little to no effect on results	Little effect on mean clotting times or CV.

2. Sample size used for the test set and the data provenance

Sample Size for Precision Studies:
- Within-day precision: The sample size (n) for the within-day precision is not explicitly stated in the provided table. It gives a single mean, SD, and CV, suggesting multiple measurements were taken to derive these metrics.
- For Lot-to-lot precision: "n = 30 each" is stated, meaning 30 measurements were taken for each of the three lots for both the Normal and Heparin controls. So, 30 measurements for Normal Lot 1, 30 for Normal Lot 2, 30 for Normal Lot 3, and similarly for the Heparin lots.
Data Provenance: The document does not specify the country of origin of the data. The studies appear to be retrospective analyses, conducted by the manufacturer, Cardiovascular Diagnostic, Inc., to characterize the performance of their TAS LHMT Controls.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not applicable to this submission. The device (TAS LHMT Controls) is a quality control material intended to verify the proper functioning of an analyzer and test cards. Its "ground truth" is its inherent chemical and physical properties that, when measured by the TAS system, produce expected clotting times. There are no human "experts" establishing a diagnostic ground truth for individual cases. The "ground truth" for the controls themselves (e.g., what constitutes a "normal" clotting time or a "heparinized" clotting time) is established by the design of the control material to mimic these states.

4. Adjudication method for the test set

This information is not applicable. Since this device is a quality control material, there is no need for expert adjudication of results, as there would be for a diagnostic device interpreting patient samples. The measurements are objective clotting times from the control material.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This information is not applicable. This device is a quality control reagent, not an AI-assisted diagnostic tool. Therefore, MRMC studies and the concept of "human readers improving with AI" do not apply.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This information is not applicable. The device is a control material, not an algorithm. Its performance is measured through its objective chemical properties and the reproducibility of results obtained from the measurement system it is designed to control.

7. The type of ground truth used

The "ground truth" for the TAS LHMT Controls are:

Designed chemical properties: The controls are made with pig plasma and formulated to produce specific clotting times under defined conditions.
Mimicry of physiological states: The "Normal" control is designed to produce a clotting time similar to a normal individual, and the "Heparin" control is designed to mimic a patient with a moderate level of heparin. This is the intended performance characteristic that the control aims to represent.
Comparison to predicate device: The performance is also validated by comparing it to the predicate TAS HMT controls, ensuring "no significant differences" in performance.

8. The sample size for the training set

This information is not applicable. This is a quality control reagent, not a machine learning or AI-based device that requires a "training set." The controls are manufactured based on established chemical formulations and tested for consistency and performance.

9. How the ground truth for the training set was established

This information is not applicable for the same reasons as #8.

Summary

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K 981178

APR 2 7 1998

וחוקים חיים חיים ו

510(k) Summary

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and CFR 807.92.

The assigned 510(k) number is __

Submitted by:

Cynthia Pritchard, Ph.D. Director of Test Development

Address:

Cardiovascular Diagnostic, Inc. 5301 Departure Drive Raleigh, NC 27616

1-800-247-4234 Phone:

1-919-954-9932 Fax:

Cynthia Pritchard, Ph.D. Contact: Director of Test Development

Peter Scott VP of Quality Assurance and Regulatory Affairs

Date of Summary: March, 1998

PA
class II

SK-36

5301 Departure Drive, Raleigh, North Carolina 27616, (919) 954-9871 FAX NUMBER (919) 954-9932

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Summary of Safety and Effectiveness Information TAS LHMT Controls

Trade name: Thrombolytic Assessment System Low Range heparin Management Test Controls (TAS LHMT controls)

Common Name: in vitro coagulation controls

Classification Name: systems for in vitro coagulation studies, automated or semiautomated instruments and associated reagents and controls used to perform a series of coagulation studies and coagulation factor assays (Class II. 21 CFR864.5425)

Predicate Device: TAS LHMT Controls provided results that compared well with other legally marketed controls when used to test the operation of the TAS Analyzer and test cards. TAS LHMT Controls are substantially equivalent to TAS HMT controls (CVDI), in performance and in intended use, but are specifically to be used with the TAS Analyzer and TAS LHMT cards. The TAS HMT controls are used with the TAS instrument and TAS HMT cards, which are to be used with noncitrated blood and citrated blood and plasma samples, to determine the integrity of the reagent/instrument system.

Description of the Device: The controls for TAS LHMT cards consist of two separate vials. One was designed to mimic a sample from a normal individual, and the second to mimic a sample from a patient with a prolonged clotting time due to administration of heparin. These controls are made with pig plasma. To make the controls as easy to use as possible for point-of-care testing, we chose the patented packaging system of Medtox, (Burlington, NC). This consists of a closed, crushable glass ampoule containing lyophilized plasma which is inside a plastic sleeve. The sleeve contains water for diluent and has a capped dropper top with a filter in the tip (to remove glass shards from the sample). The entire assembly is shrink wrapped with a label and plastic seal. To use, the ampoule is crushed inside the plastic sleeve, which allows the diluent to mix with the Ivophilized plasma. The mixture is reconstituted by shaking or vortexing the capped vial. The plastic seal and cap are removed and three drops of plasma suspension are discarded into a biohazard waste container (to eliminate the dilution effect of the diluent that is contained in the filter). A drop of the plasma suspension is added to a TAS LHMT card in an analyzer. The rest of the test procedure and the manner of signal production is identical to that for a patient sample.

Intended Use: The new TAS LHMT Controls are intended to be used with the TAS Analyzer and the TAS LHMT card to provide a method for quality control of the system. The controls produce clotting times which must be within accepted.

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Summary of Safety and Effectiveness Information TAS LHMT Controls

standard ranges, to indicate that the analyzer and test cards are functioning properly and thereby help assure the accuracy of TAS LHMT results. The controls are substantially equivalent in intended use to other controls used in coaqulation assays.

Characteristic	TAS LHMT Control	TAS HMT Control
Intended use	assure performance of systemby functional testing	same
For use with	TAS LHMT cards	TAS HMT cards
coaqulation test system	citrated	citrated
Format	glass ampoule in plastic sleeve	same
Reagent	lyophilized plasma	same
Diluent	water plus antifoam	same
Source	pig	human
Reaction	formation of a fibrin clot	same
Results	clotting time (seconds)	same
Interpretation of results	system OK if clotting timesare within set limits	same

Comparison of the TAS LHMT Controls to the Marketed Controls

There were no significant differences in the performance of the TAS LHMT Controls and the TAS HMT controls used as the predicate device. The normal control produces a clotting time like that of a normal individual; the heparin control mimics the response of a patient given a moderate level of heparin. The method of packaging the TAS controls for HMT and LHMT are the same, to make them more "user-friendly" for point-of-care testing. With this system, an operator does not have to search for a pipetting device and reagent-grade water for reconstitution, and does not have to wait for the reagent to reconstitute.

TAS LHMT Controls are stable for at least 6 weeks of storage at room temperature (20-25°C) indicating a probable refrigerator stability of at least six months. Reconstituted vials are stable for five minutes.

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Summary of Safety and Effectiveness Information

TAS LHMT Controls

Within day precision	LHMT cards
	mean (sec)	SD	CV (%)
Normal	151	1.7	1.1
Heparin	296	9.8	3.3

Lot to lot precision (n = 30 each)

	LHMT cards
	mean (sec)	SD	CV (%)
Normal	1	152	3.5	2.3
	2	153	1.9	1.3
	3	153	1.5	1.0
Heparin	1	293	10.8	3.7
	2	296	13.0	4.4
	3	293	16.7	5.7

Nonclinical Performance Data:

Freezing the intact vials has little effect on the performance of these controls; there was no significant difference in mean or CV produced by any of the controls stored at -80°C compared to vials stored in the refrigerator. Heating intact vials to 37°C for several days however, will cause an increase in the mean clotting time on LHMT cards. The angle at which drops from the control vials are dispensed has little effect on the mean clotting times or the CV of the results.

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Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three heads facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" is arranged in a circular fashion around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

APR 27 1998

Cynthia Pritchard, Ph.D. Executive Director of Development Cardiovascular Diagnostics Inc. 5301 Departure Drive Raleigh, North Carolina 27616

K981178 Re : TAS LHMT Controls Requlatory Class: II Product Code: GGN Dated: April 1, 1998 Received: April 1, 1998

Dear Dr. Pritchard:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions The general controls provisions of the Act of the Act. include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval); it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice reguirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP requlation may result in regulatory In addition, FDA may publish further announcements action. Please note: concerning your device in the Federal Register. this response to your premarket notification submission does not affect any obliqation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

sincerely yours,
Steven Litman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page _ of _

510(k) Number (if known): 4 MT contro Device Name:

Indications For Use:

Iatrided for use with the TAS analyzer
and TAB LHMT cards to provide a
method for quality control of the

oyoted!

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K981178

Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)

Regulation Number and Section

§ 864.5425 Multipurpose system for in vitro coagulation studies.

(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.